Multiwell microelectrode array with optical stimulation

Abstract

An electro-optical stimulation and recording system is disclosed, including a substrate and a plurality of wells coupled to the substrate. The system also includes at least one electrode set disposed proximate a respective one of the plurality of wells, wherein the electrode set comprises at least one electrode configured to collect an electric signal associated with at least a portion of the respective well. The system also includes a light-emitting element set corresponding to a respective one of the wells and configured to deliver optical stimulation to at least a portion of the respective well.

What is claimed is: 
     
       1. An electro-optical stimulation and recording system, comprising:
 a substrate; 
 a plurality of wells coupled to the substrate; 
 at least one electrode set disposed proximate a respective one of the plurality of wells, wherein the electrode set comprises at least one electrode configured to collect an electric signal associated with at least a portion of the respective well; 
 at least one light-emitting element set corresponding to the respective one of the plurality of wells and configured to deliver optical stimulation to at least a portion of the respective well. 
 
     
     
       2. The system of  claim 1 , wherein the at least one electrode is further configured to deliver electric stimulation to at least a portion of the respective well. 
     
     
       3. The system of  claim 1 , wherein the at least one electrode set further comprises at least one electrode configured to deliver electric stimulation to at least a portion of the respective well. 
     
     
       4. The system of  claim 1 , further comprising a plurality of light-emitting element sets, wherein at least a first of the light-emitting element sets is configured to be illuminated independently of at least a second of the light-emitting element sets. 
     
     
       5. The system of  claim 1 , wherein the at least one light-emitting element set is disposed within a wall of the respective well, disposed within the substrate, disposed within a lid configured to couple to the respective well, disposed within the bottom of the respective well, disposed between the substrate and the respective well, disposed beneath the respective well, or disposed above the respective well. 
     
     
       6. The system of  claim 1 , wherein the plurality of wells and the substrate from a multiwell plate, and wherein the at least one light-emitting element set is operably coupled to an optical stimulation module, said optical stimulation module configured to detachably couple to the multiwell plate. 
     
     
       7. The system of  claim 6 , wherein the optical stimulation module is configured to couple to the multiwell plate such that the optical stimulation module is located above the multiwell plate. 
     
     
       8. The system of  claim 6 , wherein the substrate is transparent, and wherein the optical stimulation module is configured to couple to the multiwell plate such that it provides optical stimulation via the base of the respective well. 
     
     
       9. The system of  claim 8 , further comprising a lid disposed between the at least one light-emitting element set and the plurality of wells, wherein the lid is coated with reflective material. 
     
     
       10. The system of  claim 6 , wherein the at least one light-emitting element set is integrated into an electrophysiological recording system. 
     
     
       11. The system of  claim 6 , wherein the optical stimulation module comprises a heat sink for dissipating heat. 
     
     
       12. The system of  claim 1 , further comprising a transparent, electrically conductive layer of indium tin oxide (ITO) between the at least one light-emitting element set and the respective well. 
     
     
       13. The system of  claim 1 , further comprising a lid disposed between the at least one light-emitting element set and the plurality of wells. 
     
     
       14. The system of  claim 13 , wherein the lid comprises a plurality of lenses configured to influence light traveling through the lid. 
     
     
       15. The system of  claim 1 , wherein at least one of the plurality of wells comprises curved walls and/or reflective material configured to concentrate light, shape light, and/or block bleed-through of light between adjacent wells. 
     
     
       16. The system of  claim 1 , wherein the at least one light-emitting element set provides a wavelength and light intensity suitable for activating opsins used in optogenetics methodologies. 
     
     
       17. A method for large-scale in vitro testing of cell cultures, the method comprising:
 providing a control signal for causing a light-emitting element to emit light in an illumination pattern, the light-emitting element disposed proximate a well of a multiwell plate; 
 detecting, via an electrode disposed proximate the well, a signal associated with at least a portion of the well; 
 analyzing the detected signal; and 
 outputting information indicative of the analysis. 
 
     
     
       18. The method of  claim 17 , further comprising:
 comparing the detected signal with benchmark data; 
 determining, based on the comparison, that adjustment of the illumination pattern is required; and 
 modifying the illumination pattern based on the determination. 
 
     
     
       19. The method of  claim 17 , wherein the illumination pattern includes at least one of an amplitude of a light signal, a wavelength of a light signal, and a configuration of a pulse train associated with a light signal delivered to the well. 
     
     
       20. The method of  claim 17 , wherein the control signal is configured to excite opsins of a sample within the well to the extent necessary to alter cell activity or excitability, change protein expression, and/or alter cellular growth or development. 
     
     
       21. An electro-optical stimulation and recording system, comprising:
 an electrode set disposed proximate a first well and comprising a first electrode configured to collect an electric signal associated with at least a portion of the first well; 
 a first light-emitting element set configured to deliver optical stimulation to at least a portion of the first well; and 
 a processor, configured to:
 provide a first control signal for causing a first light-emitting element to emit light at a first illumination pattern; and 
 detect, via the first electrode, a first signal associated with at least a portion of the first well. 
 
 
     
     
       22. The system of  claim 21 , wherein the processor is further configured to:
 provide a second control signal for causing a second light-emitting element to emit light at a second illumination pattern, wherein the second light-emitting element is disposed proximate a second well, and wherein the first and second light-emitting elements are configured to be illuminated independently of one another; and 
 detect, via a second electrode, a second signal associated with at least a portion of the second well. 
 
     
     
       23. The system of  claim 21 , wherein the processor is further configured to:
 compare the detected first signal with respective first benchmark data; 
 determine, based on the comparison, that adjustment of the first illumination pattern is required; and 
 modify the first illumination pattern based on the determination. 
 
     
     
       24. The system of  claim 21 , wherein the processor is further configured to display, on a user interface, a representation of the detected first signal. 
     
     
       25. The system of  claim 21 , wherein the processor is further configured to display, on a user interface, a representation of the first control signal. 
     
     
       26. The system of  claim 21 , wherein the processor is further configured to display, on a user interface, representations of the first control signal and the detected first signal. 
     
     
       27. The system of  claim 21 , wherein the processor is further configured to display, on a user interface, representations of the first control signal corresponding to a color, intensity, duration, timing, and/or location of light emitted with respect to the first well. 
     
     
       28. The system of  claim 21 , wherein the processor is further configured to update optical stimulation parameters based on metrics derived from the detected first signal.